This proposal represents a concerned effort to study the determinates of pregnancy-induced refractoriness of the mammary gland to chemical carcinogenesis. Results from our initial studies of the past two years have indicated that the mechanism(s) that act to protect the mammary gland against carcinogenesis appear to reside in the host, rather than in the mammary gland per se. We propose to carry out an in-depth investigation in order to elucidate the host factor(s) that may be responsible for induction of refractoriness in parous rats, since we believe that such studies may lead to an understanding of how pregnancy confers protection of the mammary gland against the effect of a chemical carcinogen. We will first establish the presence of host factor(s) by cross-transplantation experiments. Since pregnancy is known to cause profound endocrinological changes in the body of the mother, our second objective would be to determine if the refractoriness may be due to some "permanent" endocrinological changes resulting from pregnancy. Finally, we wish to investigate the possibility that since the fetus is an effective "allotransplantation" and fetoplacental tissue has been shown to secrete known oncofetal antigens, pregnancy may induce immunological changes in the parous rat which would act to prevent the development of tumors in the mammary gland.